Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms 1 . Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts 2 , 3 . However, the mechanistic basis of this microbiota–brain signalling and its physiological relevance are largely unknown. Here we show that in Caenorhabditis elegans , the neuromodulator tyramine produced by commensal Providencia bacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine β-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis in Providencia , and show that these genes are necessary for the modulation of host behaviour. We further find that C. elegans colonized by Providencia preferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism. A neuromodulator produced by commensal Providencia bacteria that colonize the gut of Caenorhabditis elegans mimics the functions of the cognate host molecule to manipulate a sensory decision of the host.

中文翻译：

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肠道细菌产生的神经递质调节宿主的感觉行为

动物与包括微生物在内的多种生物体的复杂群落以共生、致病或互利关系共存 1 。一些细菌产生生物活性神经递质，此前已提出这些神经递质可以调节宿主的神经系统活动和行为 2 , 3 。然而，这种微生物群-大脑信号传导的机制基础及其生理相关性在很大程度上尚不清楚。在这里，我们表明，在秀丽隐杆线虫中，定植于肠道的共生普罗维登斯细菌产生的神经调节剂酪胺绕过了宿主酪胺生物合成的要求并操纵了宿主的感觉决策。细菌产生的酪胺可能被宿主酪胺β-羟化酶转化为章鱼胺。章鱼胺反过来又靶向 ASH 伤害性神经元上的 OCTR-1 章鱼胺受体，以调节厌恶的嗅觉反应。我们鉴定了普罗维登西亚酪胺生物合成所需的基因，并表明这些基因对于调节宿主行为是必需的。我们进一步发现，普罗维登斯菌定殖的线虫在食物选择测定中优先选择这些细菌，并且这种选择偏差需要细菌产生酪胺和宿主章鱼胺信号传导。我们的结果表明，肠道细菌产生的神经递质模仿同源宿主分子的功能，超越宿主对感觉决定的控制，从而促进宿主和微生物的适应性。由定殖于秀丽隐杆线虫肠道的共生普罗维登斯细菌产生的神经调节剂模仿同源宿主分子的功能来操纵宿主的感觉决定。